The ELISA assay has been automated and the apoA-I, A-II, and B assays are presently being run while the apoC-II and E assays are being developed. Apolipoprotein E is a polymorphic protein with 3 common isoforms, apoE2, E3, and E4, with apoE2 being catabolized the slowest and apoE4 the fastest in humans. ApoE2 has two reactive cysteines while apoE4 has these cysteines replaced with arginines. The slow metabolism of apoE2 was determined to be due to both the charge alteration of the protein resulting from the substitution of cysteine for the arginine and the slow catabolism of the apoE2 disulfide dimers. ApoA-I was isolated from a subject with hypoalphalipoproteinemia associated with a restriction fragment length polymorphism linked to the apoA-I gene. The catabolic rate of this apoA-I was normal indicating that the defect in this subject is either in the synthesis rate of apoA-I or in another gene closely linked to the apoA-I gene. Tangier disease is characterized by rapid catabolism of HDL but macrophages from Tangier disease subjects were determined to be normal for HDL binding, internalization, degradation, and resecretion. Further investigations into the etiology of the rapid HDL catabolism in Tangier disease are being pursued. ApoC-II exists in plasma in a pro and mature form. The metabolism of both forms were studied and it was determined that both forms were catabolized relatively rapidly and at the same rate. In addition, there was a very slow conversion of the pro form to mature form of apoC-II. Abetalipoproteinemia is characterized by a virtual absence of apoB in plasma. By utilizing sensitive methods for the detection of apoB mRNA and protein, increased amounts of apoB mRNA were assayed in liver from two study subjects and apoB protein was detected in the liver and plasma from two subjects. This indicates that in some subjects with abetalipoproteinemia, the defect is a translational or post-translational abnormality that leads to the inability to secrete apoB and apoB containing lipoproteins.